The ongoing rise in costs and morbidity associated with occupational musculoskeletal disorders (MSDs) demands the investigation of known risk factors for injury. Repetition of movement, forceful loading and their combination (repetitive loading) are risk factors for MSDs. These happen to be some of the few modifiable risk factors for MSDs of the hand and other joints. This project proposes to use an in vivo animal model of repetitive finger joint loading to elucidate the relative risks of these factors (repetition and combined force and repetition). Finger joint loading is used to simulate hand intensive tasks found in the workplace to test the following hypothesis: The combination of force and repetition is an occupational risk factor for MSD. This project will quantify the structural and molecular changes in joint tissues due to repetitive loading. And finally, this project will determine the threshold of repetitive loading in a dose-response study. The long term goals of this study are to 1) determine the relative contributions of individual biomechanical characteristics of finger joint loading, namely repetition, force level, and duration of exposure; and 2) demonstrate causality between these biomechanical risk factors, cellular response, tissue damage, and injury. The results of this mechanobiology project will lead to guidelines for effective interventions of MSDs of the hand joints such as osteoarthritis (OA) or degenerative joint disease (DJD). This project directly addresses the National Occupational Research Agenda (NORA) in 1) developing a quantitative dose-response model identifying dose-response relationships, 2) determining whether the injury response of the tissue has more to do with repetition of loading or level of peak load, and 3) identifying the ultrastructural injury and biochemical alterations associated with physical loading.